PB1980: MULTIPLE MYELOMA: ADOPTING MRD BY NEXT GENERATION FLOW CYTOMETRY (NGF) AND FUNCTIONAL IMAGING GUIDED CONSOLIDATION INTO CLINICAL ROUTINE
Authors: D. Boeckle, P. Tabares, X. Zhou, S. Schimanski, M. J. Steinhardt, M. Bittrich, E. Seebacher, M. Ulbrich, A. Wilnit, C. Metz, A. Heidemeier, T. Bley, R. Werner, A. Buck, H. Einsele, M. Kortüm, A. Beilhack, L. Rasche
Journal: HemaSphere (2022)

Background: Minimal residual disease (MRD) detection by NGF and next generation sequencing gains is gaining increasing importance as an endpoint in clinical studies to determine deep responses beyond traditional immunohistochemical complete remission. However, little is known about the value of combining NGF with functional imaging and its role for MRD based consolidation strategies in clinical routine. Aims: The aim of the study was to investigate the role of MRD and functional imaging in clinical routine in MM. In addition, we report our real-world experience with an MRD-guided consolidation strategy. Methods: We included 102 patients with both newly diagnosed (ND) (n=57) and relapsed/refractory (RR) MM (n=45) that achieved serological response of VGPR or better. Among NDMM patients, 92% (n=52) underwent stem cell transplantation (SCT) after induction and 27% of RRMM patients received a salvage transplantation. MRD assessment by NGF was available in all patients. Bone marrow samples were collected between July 2019 and May 2021 and analyzed according to the Euroflow guidelines at a sensitivity level of 10-6. We performed functional imaging in 78 patients with either FDG positron emission tomography or diffusion-weighted magnetic resonance imaging within a median of 1 day after NGF assessment. Results: 51 patients (50%) were negative on MRD assessment by NGF. We observed higher rates of MRD-negativity in subjects with a serological response of CR/sCR or better versus VGPR (59% versus 34%, p=0.01), OR=2.8). Furthermore, we combined NGF results with functional imaging: MRD-negativity on both NGF and functional imaging (double-negativity) was achieved in 45% of patients. 8% and 40% of patients were negative on either NGF or imaging respectively. In some patients, imaging was the only technique applied to detect residual disease. We observed imaging positivity despite negativity on NGF more often in heavily pretreated patients (≥ 4 previous lines) compared to NDMM (p<0.01). In detail, we found a number needed to scan for imaging-only positive patients of 40, 8 and 3 in NDMM, relapsed, and heavily pretreated RRMM, respectively. MRD-triggered consolidation therapy was initiated in 29 patients with 72% responding to treatment and a MRD conversion rate of 51%. Interestingly, MRD-triggered consolidation (mostly after SCT) led to a superior progression free survival (Figure 1) when compared to standard Lenalidomide maintenance on MRD or imaging positive patients (p=0.04). Subjects achieving double-negativity after standard of care treatment were excluded from this analysis. Image:Summary/Conclusion: Our data indicate that combining NGF with functional imaging is beneficial particularly in heavily pretreated MM patients to rule out residual disease. Furthermore, our real-world experience gives evidence that MRD-based consolidation may be used to improve PFS of patients being MRD positive following SCT. Further studies investigating these issues in a randomized prospective fashion are highly warranted.